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Blood, 15 February 2008, Vol. 111, No. 4, pp. 1933-1941.
Prepublished online as a Blood First Edition Paper on November 27, 2007; DOI 10.1182/blood-2007-02-074120.


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Submitted February 15, 2007
Accepted November 20, 2007

Short-term BMP-4 treatment initiates mesoderm induction in human embryonic stem cells

Pengbo Zhang, Jian Li, Zhijia Tan, Chengyan Wang, Ting Liu, Lin Chen, Jun Yong, Wei Jiang, Xiaomeng Sun, Liying Du, Mingxiao Ding, and Hongkui Deng*

Key Laboratory of Cell Proliferation and Differentiation of the Ministry of education, College of Life Sciences, Peking University, Beijing, China
Laboratory of Chemical Genomics, Shenzhen Graduate School of Peking University, Shenzhen, China

* Corresponding author; email: hongkui_deng{at}pku.edu.cn.

Human embryonic stem cells (hES cells) have unlimited self-renewal capacity, and can differentiate into most, if not all, possible cell types. This unique property makes them valuable not only for investigation of early developmental processes, but also for regenerative medicine. Mesoderm-derived cardiac cells and hematopoietic cells both have the potential for various therapeutic applications. However, efficient induction of hES cell differentiation into mesoderm remains a challenge. Here, we showed that treatment of hES cells with bone morphogenetic protein-4 (BMP-4) exhibited differential effects: long-term treatment results in trophoblast and extra-embryonic endoderm differentiation, while short-term treatment can promote early mesoderm induction. The induction of mesoderm in hES cells occurs at a high efficiency as measured using several markers such as brachyury, Wnt3, and Mixl1 expression. Moreover, these mesodermal progenitor cells can differentiate into cardiac and hematopoietic lineages in vitro. Further analysis showed that the mesoderm-inducing capacity of BMP-4 requires endogenous FGF and TGF-{beta}/Nodal/activin signaling activities. Thus, our results uncover a novel role for BMP-4 in regulation of hES cell differentiation, and should provide insights into the mechanism of mesoderm induction in hES cells.


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S. Takei, H. Ichikawa, K. Johkura, A. Mogi, H. No, S. Yoshie, D. Tomotsune, and K. Sasaki
Bone morphogenetic protein-4 promotes induction of cardiomyocytes from human embryonic stem cells in serum-based embryoid body development
Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1793 - H1803.
[Abstract] [Full Text] [PDF]



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